Assessing β-Amyloid-Induced NLRP3 Inflammasome Activation in Primary Microglia

Schnaars, Mareike; Beckert, Hannes; Halle, Annett

doi:10.1007/978-1-62703-523-1_1

Cited by 26 publications

(19 citation statements)

References 10 publications

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“…The innate immune response resulting in inflammation depends upon recognition of pattern-recognition receptors (PRRs). PRRs are expressed mainly in immune and inflammatory cells such as monocytes, neutrophils and antigen-presenting cells (APCs) including macrophages and dendritic cells 34,35 . The association shown in the ingenuity pathway suggests that activation of PRRs resulted, leading to the induction of the inflammatory response with proinflammatory cytokines and type I interferons (interferon-α and interferon-β) 36 .…”

Section: Discussionmentioning

confidence: 99%

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Kahal

Halama

Aburima

et al. 2020

Sci Rep

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Intensive diabetes control has been associated with increased mortality in type 2 diabetes (T2DM); this has been suggested to be due to increased hypoglycemia. We measured hypoglycemia-induced changes in endothelial parameters, oxidative stress markers and inflammation at baseline and after a 24-hour period in type 2 diabetic (T2DM) subjects versus age-matched controls. Case-control study: 10 T2DM and 8 control subjects. Blood glucose was reduced from 5 (90 mg/dl) to hypoglycemic levels of 2.8 mmol/L (50 mg/dl) for 1 hour by incremental hyperinsulinemic clamps using baseline and 24 hour samples. Measures of endothelial parameters, oxidative stress and inflammation at baseline and at 24-hours post hypoglycemia were performed: proteomic (Somalogic) analysis for inflammatory markers complemented by C-reactive protein (hsCRP) measurement, and proteomic markers and urinary isoprostanes for oxidative measures, together with endothelial function. Between baseline and 24 -hours after hypoglycemia, 15 of 140 inflammatory proteins differed in T2DM whilst only 1 of 140 differed in controls; all returned to baseline at 24-hours. However, elevated hsCRP levels were seen at 24-hours in T2DM (2.4 mg/L (1.2-5.4) vs. 3.9 mg/L (1.8-6.1), Baseline vs 24-hours, P < 0.05). In patients with T2DM, between baseline and 24-hour after hypoglycemia, only one of 15 oxidative stress proteins differed and this was not seen in controls. An increase (P = 0.016) from baseline (73.4 ng/mL) to 24 hours after hypoglycemia (91.7 ng/mL) was seen for urinary isoprostanes. Hypoglycemia resulted in inflammatory and oxidative stress markers being elevated in T2DM subjects but not controls 24-hours after the event.While type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease 1 , strict glycemic control does not result in obvious cardiovascular benefit in people with T2DM 2-4 . A link between strict glycemic control, hypoglycemia and increased cardiovascular morbidity and mortality has been observed in clinical studies 5,6 . Although the underlying mechanism remains unclear, increased inflammatory cytokines and a leukocytosis are reported after hypoglycemia 7,8 , suggesting a link between hypoglycemia and inflammation.It is well recognized that oxidative stress leads to damage of proteins and deoxyribonucleic acid (DNA) 9 and contributes to the diabetic complications of retinopathy, nephropathy, neuropathy and cardiovascular disorders 10-13 , and is directly linked to vascular inflammation, precipitating both endothelial cell dysfunction and vascular damage 14 . Oxidative stress results from excessive generation of free radicals and/or deficient defense mechanisms 15 , and leads to a disturbance of the physiological redox state 16 . The membrane associated 1

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Section: Discussionmentioning

confidence: 99%

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Kahal

Halama

Aburima

et al. 2020

Sci Rep

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“…Extensive evidence indicates that activation of the NLRP3 inflammasome is a critical process of the inflammatory response in disease progression of AD patients and APP/PS1 mice . Assembly and activation of the NLRP3 inflammasome leads to cleavage of pro‐caspase‐1 to generate active caspase‐1, which then initiates maturation and secretion of pro‐IL‐1β in the AD brain . Moreover, inhibition of NLRP3 and caspase‐1, such as through artemisinin treatment, has been shown to exert protective effects in AD pathology .…”

Section: Discussionmentioning

confidence: 99%

Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice

Feng

Wang

et al. 2018

CNS Neurosci Ther

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SummaryBackgroundActivated microglia‐mediated inflammation plays a key role in the pathogenesis of Alzheimer’s disease (AD). In addition, chronic activation of NLRP3 inflammasomes triggered by amyloid β peptide (Aβ) in microglia contributes to persistent neuroinflammation. Here, the primary goal was to assess whether Dihydromyricetin (DHM), a plant flavonoid compound, is effective therapies for AD; it is crucial to know whether DHM will affect microglial activation and neuroinflammation in APP/PS1 transgenic mice.MethodsAfter DHM was intraperitoneally injected in APP/PS1 double‐transgenic mice, we assessed the effect of DHM on microglial activation, the expression of NLRP3 inflammasome components, and the production of inflammatory cytokine IL‐1β by immunofluorescence and Western blot. To determine whether DHM play roles in the Aβ production and deposition, amyloid β protein precursor (APP) and β‐site APP cleaving enzyme1 (BACE1), as well as neprilysin (NEP), were detected by Western blot. Finally, behavior was tested by Morris Water Maze to illustrate whether DHM treatment has a significantly positive effect on ameliorating the memory and cognition deficits in AD.ResultsDihydromyricetin treatment significantly ameliorated memory and cognition deficits and decreased the number of activated microglia in the hippocampus and cortex of APP/PS1 mice. In addition, APP/PS1 mice show reduced activation of NLRP3 inflammasomes and reduced expression of NLRP3 inflammasome components. Furthermore, DHM could promote clearance of Aβ, a trigger for NLRP3 inflammasome activation, by increasing levels of NEP and shift microglial conversion to the M2‐specific agrinase‐1‐positive cell phenotype, which enhances microglial clearance of Aβ and its aggregates but not production of Aβ.ConclusionTaken together, our findings suggest that DHM prevents progression of AD‐like pathology through inhibition of NLRP3 inflammasome‐based microglia‐mediated neuroinflammation and may be a promising therapeutic drug for treating AD.

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“…The molecular signaling which triggers inflammasome assembly after SCI has been previously studied. It has been proposed that danger signals such as high plasma glucose, β-amyloid, Tolllike receptor (TLR) ligands, uric acid, and ATP induce inflammasome activation [47][48][49][50][51]. In particular, the engagement of ATP with P2X4 or P2X7 purinergic receptors induces inflammasome activation.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

Lin

Wang

2017

The Spine Journal

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Assessing β-Amyloid-Induced NLRP3 Inflammasome Activation in Primary Microglia

Cited by 26 publications

References 10 publications

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice

Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

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